Process and device for the dose dispensing of a radioactive solution

ABSTRACT

An apparatus and method for automatically dispensing a radioactive dose by filling a container, such as a vial or disposable syringe, with a required radioactive dose in a sterile environment; the apparatus being stand alone and radioactive-shielded. The apparatus further includes a control device for accurately dispensing and diluting the required radioactive dose using an online radioactivity measurement, which does not require knowledge of the volumetric radioactivity of the stock solution.

AREA OF THE INVENTION

This invention relates to apparatus used in nuclear medicine and inparticular to a means whereby a radioactive dose required can beprovided to a syringe in an automated fashion which obviates the needfor a person to actually handle the radioactive material.

BACKGROUND OF THE INVENTION

Radioactive solutions called radiotracers or radiopharmaceuticals, havefound applications in various medical fields, in particular in medicaldiagnostic and therapeutic fields. In recent years the advance ofPositron Emission Tomography (PET), which use radionuclides(radioisotopes) of significant higher radiation energy than moreconventional nuclear medicine isotopes, has raised some concerns abouthand and body radiation exposure received by the persons preparing thedose.

The dangers of ionising radiation are well known and apply to allpersons being exposed to radiation, including the staff involved in thepreparation of radioactive solutions. Dose fractionation of theradioactive solutions is usually a manual process, performed behind alead shielded screen to minimal exposure to radiation. However, theperformance of this task is time consuming, as the operator needs towithdraw by successive iterations, small volumes of the radiotracer,until he reaches the targeted dose.

After each withdrawal the needle needs to be re-capped and the syringeplaced in a dose calibrator to determine if more or less of theradioactive solution should be processed in or out of the syringe. Whenthe targeted dose has been achieved (within ±10%), the syringe may betopped up with saline to obtain a reasonable volume.

Before being released or dispatched for clinical use, the syringe isplaced again in the dose calibrator to print out the accurate doserecord. To date, very little attempt has been made by manufacturers todesign automated equipment capable of withdrawing a dedicatedradioactive dose into a disposable sterile syringe or vial.

The very few systems currently on the market are expensive and bulky andare not widely available. Other more affordable systems are either nottechnically practical or do not achieve efficient radiation protectionand need to be operated in a shielded environment. In addition, most ofthese apparatus rely on the pre-requisite knowledge of the volumetricradioactivity (Ci/mL or Bq/mL) of the stock solution to determine thecorresponding volume and hence the radioactive dose to be dispensed.

OUTLINE OF THE INVENTION

It is an object of this invention to provide an accurate means ofautomatically dispensing individual doses of a radioactive solution intovials or syringes under aseptically controlled conditions whileminimising the exposure to radiation of an operator which wouldotherwise be associated with the manipulation of radioactive solutions.

The invention in one aspect is a radioactive dose dispensing device forautomatically filling a container with a required radioactive dose in asterile environment, said device being stand alone and radiationshielded and including control means to control a mix of radioactivestock solution and dilution stock solution, the radioactivity of whichmix is monitored by radiation detection means.

The invention in a second aspect is a method of automatically dispensinga dose of a radioactive solution using a software controlled leadshielded device which includes the steps of

-   -   providing the device with a radioactive stock solution and a        dilution stock solution    -   using a computer software interface to the device to control the        dose dispensed automatically into a syringe or vial in the        device.

It is preferred that the radioactive dose dispensing device be used forfilling a disposable syringe. It is further preferred that a shieldedreceptacle be provided to receive the syringe.

It is also preferred that a fork shaped arm be provided to actuate theplunger of the disposable shielded syringe. It is further preferred thata high precision linear drive mechanism to move either the syringe orits plunger in a vertical direction.

It is preferred that a customised disposable T shaped tubing assembly beused to provide a sterile fluid pathway. It is further preferred thatpinch valves be provided to switch between the radioactive stocksolution and the dilution stock solution.

It is also preferred that the automation of the device be controlled bya programmable logic controller (PLC) in association with a radiationdetector which monitors on-line the radioactive dose passing through thetubing and being dispensed into the syringe.

It is further preferred that the PLC controls the automation tasks andrelevant mathematical calculations for dispensing a requisite dose andthat this be operable by computer means with an associated printeralthough any desired arrangement could be used.

In order that the invention may be more readily understood an embodimentof it will be described herein by way of non limiting example withreference to the accompanying drawings

BRIEF DESCRIPTION OF THE DRAWING FIGURES

FIG. 1 Shows a perspective view of the components of the radioactivedose dispensing device of the invention in its “open” orientation;

FIG. 2 Shows a cross-section though the device of the invention as shownin FIG. 1;

FIG. 3 Shows the pre assembled sterile disposable tubing kit used in thedevice;

FIG. 4 Shows the device of the invention in its “closed” orientation;

BRIEF DESCRIPTION OF AN EMBODIMENT OF THE INVENTION

The invention 100 in one embodiment is a device for the automaticfilling of disposable syringes with a radioactive solution(radiopharmaceutical) for injection or infusion into a patient.

The device 100 is a stand alone equipment that does not require anyadditional lead shielding and can be directly used on a bench or insidea conventional, unshielded, laminar flow cabinet.

The device includes a concave lead block 30 and a swinging lead lid 32designed to accommodate standard lead shielded pots 31 commonly used forthe transport of radioactive solutions. It also includes a receptacle 51that can accommodate various shapes of commercially available tungstensyringe shields and provides an easy and safe installation of thesyringe shield 52.

The device further includes a fork-shape arm 41 that can hold or releasethe plunger of the syringe and an electro-actuator that can link thelinear drive 36 to the receptacle 51, and drive up/down the syringe andits needle 55 to pierce the Luer Slip Injection Site 59.

The device provides a permanent link between the linear drive 36 and thefork-shape arm 41 and allows both the radioactive solution and thediluting solution to be drawn at a constant fluid flow rate through thetubing and into the syringe.

The Luer Slip Injection Site 59 is attached to the upper tubing assemblyand two Luer-lock fittings 61 (with needles) are attached to the lowertubes assembly (see FIG. 3 for view of the pre-assembled steriledisposable kit).

The tubing assembly is held in its appropriate position by a smallgroove and a dedicated shaped recess 2 to accurately position the LuerSlip Injection Site 59, in regard to the needle 55.

The device is provided with both radioactive and diluting stocksolutions which are dispensed from their respective vials 34 and 62, upto the syringe by passing through a disposable, sterile andnon-pyrogenic fluid pathway with the radioactive amount controlled by aradiation detector 63, which in this embodiment of the invention is aGeiger-Muller tube or PIN photodiode and located behind a portion of thetube assembly leading to the injection site (behind the plate holder 2).

The device is automated via a programmable PLC and is connected to acomputer serving as a user interface, and preferably is provided with aprinter to print the syringe or vial label showing the activity, date,time, batch, patient name, etc. or whatever may be required.

The dispensing of the radioactive dose is done on-line by measuring thetrue amount of radioactivity passing in front of the radiation detector63 and the total volume required into the syringe is automaticallyadjusted by dilution.

The device also includes a safety cross-evaluation of the deliveredradioactive dose which is automatically performed using the traditionalvolumetric dispensing method, and the volumetric method can also be usedas the main dispensing method.

It is further envisaged that the device of the invention may include abuilt-in sterile air flow, designed to allow the device to be operatedon a bench in a conventional room but still maintaining full compliancewith a 3.5 class (A class) dispensing environment, characterized by asterile air flow directed towards the Luer Slip Injection Site 59 andneedle 55.

It is also envisaged that in another embodiment of the invention asterile disposable double check-valve could be located between thesyringe 53 and needle 55, or underneath the Luer Slip Injection Site 59to allow the transfer of an accurate dose of radioactive solutionthrough a tube, to externally located vials or containers.

Operation of the Device

When the device is being operated the user opens the door 9 of thedevice and installs a new tubing kit 57 onto the tubing holder 2. TheLuer Slip Injection Site 59 attached to the upper T-shape tube is slidinto the appropriate recess and both needles 61 attached to the lowerT-shape tubes are fed through each lead channel and connected to theradioactive stock solution 34 and the dilution stock solution 62.

The user then rotates the lid 32 and closes the door 9 and introduces adisposable syringe 53 with its appropriate needle 55 into a tungstensyringe shield 52. At this point the needle is un-capped and thetungsten syringe shield is placed onto the receptacle 51 on the frontface of the device. The operator then enters on the computer therequested radioactive dose and total volume.

The device lowers the receptacle 51 enabling the syringe to pierce theLuer Slip Injection Site with the needle. The filling sequence willautomatically dispense the desired radioactive dose into the syringe anddilute it to match the requested volume by actuation of the syringeplunger. Once the syringe has been filled (less than one minute), thesyringe and syringe shield are lifted away from the Luer Slip InjectionSite, and the syringe and syringe shield is removed from the device andneedle re-capped. At the end of the process, a syringe label is printedwith the appropriate dose data.

SUMMARY OF THE EMBODIMENT OF INVENTION

Traditionally the accurate knowledge of the volumetric radioactivity(specific activity: Ci/mL or Bq/mL) of a radioactive stock solution isrequired for the accurate dispensing of any radioactive dose.

For example, a dose of 3 mCi (111 MBq) of a radioactive solution with avolumetric radioactivity of 50 mCi/mL (1850 MBq/mL) will be preciselyachieved by dispensing a volume of 0.06 mL. However, volumetricradioactivity of solutions is not always determined with great accuracyat the time of the manufacturing of the product, and post measurement ofthe volumetric radioactivity at the customer site is regarded as acritical operation.

The invention has the novel feature in that it can accurately dispense arequested radioactive dose without any knowledge of the volumetricradioactivity of the stock solution by an on-line radioactivitymeasurement and without exposing an operator to the radiation.

In the invention, a radiation detector 63 being a Geiger-Muller tube, aPIN photodiode or other fast measuring device is located behind aportion of the tubing leading to the injection site 59 and then to thesyringe 53. The radiation detector continuously monitors the radioactivedose passing through the tube and into the syringe at a very constantliquid flow rate and the PLC 11 determines the appropriate switchingsequence of the valves to dispense the requested dose and volume.

The program also calculates online the corresponding radioactivitycontained in the dead volume of the tubing which will be inevitablyadded-on during the dilution phase of the syringe filling. Thatcorresponding radioactivity is subtracted from the required dose by thePLC 11 to identify the amount of radioactivity allowed to pass theradiation detector 63. At the end of the filling process, the sum of theamount of activity allowed to pass by the detector before the dilutionphase and the resultant activity gained during the dilution phase due tothe dead volume of the tubing kit, translates to the required dose.

Below is the formula used to determine how much of the stock solutionneeds to be drawn-up into the syringe to achieve the desired dose (thiscalculation is performed continuously during the filling process):

-   -   Let RD=Requested dose    -   ADV=Activity contained in the dead volume of the tubing    -   RMT=Radioactivity measured passing through the tubing    -   VA=Volumetric activity of the stock solution    -   DV=Dead volume of the tubing    -   SA=Volumetric radioactivity    -   VSW=Volume of stock solution withdrawn from vial

Therefore the radioactive amount of stock solution to draw-up intosyringe:  = RD − ADV = RD − (DV × SA) = RD − (DV × (RMT/(VSW − DV))

Using the above method of filling a syringe with a radioactive solution,it is not necessary to know the specific activity of the stock solutionprior to the filling process, as it is calculated during the fillingprocess.

The accuracy of the dose dispensed is a function of the volumetricradioactivity of the radioactive stock solution, and experiments haveshown accuracy better than 5% for volumetric radioactivity in the rangeof 0-50 mCi/mL (0-1850 MBq/mL) and better than 10% for volumetricradioactivity in the range of 50-100 mCi/mL (0-3700 MBq/mL).

The invention lies in an automated means of preparing a dose of aradiopharmaceutical into a disposable syringe under computer control bymeans of a radiation detector to determine the radioactive dosage anddilution by a non radioactive solution to achieve a desired volume. Bythis means such a dose can be prepared without unnecessary radiationexposure occurring to the person preparing the dose.

The precise components of the apparatus of the invention may be variedprovided they achieve the method of the invention as described. It isfurther envisaged that other embodiments of the invention will exhibitany number of and any combination of the features of those previouslydescribed and whilst we have described herein one specific embodiment ofthe invention it is to be understood that variations and modificationsin this can be made without departing from the spirit and scope thereof.

1-10. (canceled)
 11. A radioactive dose dispensing apparatus forautomatically filling a container with a required radioactive dose in asterile environment, comprising: means for radiation shielding of saidradioactive dose dispensing apparatus; means for controlling a mix ofradioactive stock solution and dilution stock solution; and, means fordetecting radioactivity of said mix of radioactive stock solution anddilution stock solution.
 12. The radioactive dose dispensing apparatusaccording to claim 11, wherein said container is plunger-operateddisposable syringe.
 13. The radioactive dose dispensing apparatusaccording to claim 12, further comprising a shielded receptacle forreceiving plunger-operated disposable syringe.
 14. The radioactive dosedispensing apparatus according to claim 12, further comprising drivemeans for actuating said plunger-operated disposable syringe.
 15. Theradioactive dose dispensing apparatus according to claim 14, whereinsaid drive means is a linear drive mechanism for actuating saidplunger-operated disposable syringe.
 16. The radioactive dose dispensingapparatus according to claim 12, further comprising a programmable logiccontroller for automating said radioactive dose dispensing apparatus andcalculating a required dose, said programmable logic controller operablein combination with a radiation detector for controlling the radioactivedose being dispensed into said plunger-operated disposable syringe. 17.The radioactive dose dispensing apparatus according to claim 16, whereinprogrammable logic controller is operable via a computer interface. 18.The radioactive dose dispensing apparatus according claim 11, furthercomprising a disposable tubing assembly for providing a sterile fluidpathway for the dilution stock solution.
 19. The radioactive dosedispensing apparatus according claim 11, further comprising pinch valuesfor switching between the radioactive stock solution and the dilutionstock solution.
 20. A method for automatically dispensing a dose ofradioactive solution using a software-controlled lead shieldedapparatus, comprising the steps of: providing a radioactive stocksolution for said software-controlled lead shielded apparatus; providinga dilution stock solution for said software-controlled lead shieldedapparatus; and, controlling a dose of radioactive solution dispensedautomatically into a syringe or vial via a computer software interface.